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Biomedical subjects

J Vick

Publications and source records attributed to J Vick.

At least 19 recordsLinked to original sources

Synergism between dipyridamole and cisplatin in human ovarian carcinoma cells in vitro.

Dipyridamole (DPM), a nucleoside membrane transport inhibitor, enhanced the cytotoxicity of cisplatin (DDP) for human ovarian carcinoma 2008 cells by a factor of 4.7 +/- 0.4-fold (mean +/- SD) and for the 10-fold DDP-resistant 2008/C13*5.25 subline by a factor of 5.8 +/- 2.7-fold. This interaction was shown to be truly synergistic by isobologram and median effect analysis. DPM enhancement of DDP cytotoxicity was schedule dependent; it was greatest when cells were exposed to DPM continuously during and following a 1-h exposure to DDP and less pronounced when DPM exposure was limited to pretreatment or concurrent treatment only. DPM increased DDP uptake in a concentration-dependent manner as measured with both [195mPt]-DDP and the DDP analogue [3H]-cis-dichloro(ethylenediamine) platinum. Nitrobenzylthioinosine, another nucleoside membrane transport inhibitor, did not enhance DDP cytotoxicity or uptake at concentrations that produced equivalent degrees of inhibition of [3H]uridine uptake. DPM did not interact synergistically through an increase in cellular cyclic AMP levels. DPM did not increase trypan blue or propidium iodide uptake, or change cell size, indicating that it did not nonspecifically increase membrane permeability. We conclude that DPM interacts synergistically with DDP and that, while an increase in DDP uptake is one component of the mechanism of this interaction, there are additional components since maximal effect was observed only with prolonged DDP exposure.

Carcinoma

Cardiotoxic effects of the combined use of caffeine and isoproterenol in the minipig.

Beta agonists such as isoproterenol are widely used in the treatment of acute asthmatic attacks. It would not be unexpected that some patients receiving isoproterenol might have ingested caffeine as an over-the-counter drug or beverage. This study explores the possible interaction between these two drugs. Anesthetized minipigs were injected with 0.5 mg/kg caffeine iv followed by a 10-min infusion of 1 microgram/kg.min isoproterenol. Heart rate, EKG, respiration, and blood pressure were recorded continuously and the animals were sacrificed at 72 h. The two drugs in combination produced subtle changes in heart rate and blood pressure with significant alteration in the EKG tracing (premature ventricular contractions and extrasystoles). These changes persisted for 8 to 24 h. At autopsy both gross and microscopic lesions were noted in 10 of the 13 minipig hearts receiving the combination of drugs. This was not true of the six minipigs given only caffeine or the eight minipigs receiving only the infusion of isoproterenol. No changes in EKG tracings or pathologies were noted with caffeine and only two of eight animals infused with isoproterenol showed any lesions. Results indicate that doses of caffeine equivalent to that expected from drinking a cup of coffee appear to increase the toxicity of isoproterenol to a point that EKG changes and myocardial pathologies are observed.

Animals

Role of the sympathetic nervous system in daunomycin-induced arrhythmia in the monkey.

1. Infusion of daunomycin 50 mg/kg in the monkey consistently induced ventricular arrhythmias which were not influenced by bilateral vagotomy.2. A central sympathetic component to the arrhythmias was suggested because spinal transection, ganglionic blockade or bilateral stellate ganglionectomy prevented any alterations in the e.c.g.3. Bilateral adrenalectomy or splanchnic nerve section protected three of six animals. This source of catecholamines may not be necessary in every case to initiate the arrhythmia.4. Guanethidine was a relatively ineffective antiarrhythmic agent. Timing appears to be important with this agent.5. Pargyline, by monoamine oxidase inhibition or other mechanisms, significantly lowered the arrhythmic dose of daunomycin. Reserpine pretreatment, on the other hand, prevented any e.c.g. alterations following daunomycin.6. Phenoxybenzamine exerted significant protection which may be related to its cardiodepressant properties.7. Alterations in e.c.g. were seen in all (+)-propranolol pretreated animals, although the arrhythmic period was modified in two of three experiments. Racemic (+/-) propranolol, which exerts direct myocardium depression as well as beta-adrenoceptor blockade, was completely protective in four of five experiments. The results of the present experiments indicate that the sympathetic nervous system is intimately involved in the daunomycin arrhythmia.

Adrenalectomy